Identification of a cancer stem cell-specific function for the histone deacetylases, HDAC1 and HDAC7, in breast and ovarian cancer.

Tumours are comprised of a highly heterogeneous population of cells, of which only a small subset of stem-like cells possess the ability to regenerate tumours in vivo. These cancer stem cells (CSCs) represent a significant clinical challenge as they are resistant to conventional cancer therapies and play essential roles in metastasis and tumour relapse. Despite this realization and great interest in CSCs, it has been difficult to develop CSC-targeted treatments due to our limited understanding of CSC biology. Here, we present evidence that specific histone deacetylases (HDACs) play essential roles in the CSC phenotype. Utilizing a novel CSC model, we discovered that the HDACs, HDAC1 and HDAC7, are specifically over-expressed in CSCs when compared to non-stem-tumour-cells (nsTCs). Furthermore, we determine that HDAC1 and HDAC7 are necessary to maintain CSCs, and that over-expression of HDAC7 is sufficient to augment the CSC phenotype. We also demonstrate that clinically available HDAC inhibitors (HDACi) targeting HDAC1 and HDAC7 can be used to preferentially target CSCs. These results provide actionable insights that can be rapidly translated into CSC-specific therapies.

Utilization of food industry wastes for the production of zero-valent iron nanoparticles.

The proper disposal of the several types of wastes produced in industrial activities increases production costs. As a consequence, it is common to develop strategies to reuse these wastes in the same process and in different processes or to transform them for use in other processes. This work combines the needs for new synthesis methods of nanomaterials and the reduction of production cost using wastes from citrine juice (orange, lime, lemon and mandarin) to produce a new added value product, green zero-valent iron nanoparticles that can be used in several applications, including environmental remediation. The results indicate that extracts of the tested fruit wastes (peel, albedo and pulp fractions) can be used to produce zero-valent iron nanoparticles (nZVIs). This shows that these wastes can be an added value product. The resulting nZVIs had sizes ranging from 3 up to 300 nm and distinct reactivities (pulp>peel>albedo extracts). All the studied nanoparticles did not present a significant agglomeration/settling tendency when compared to similar nanoparticles, which indicates that they remain in suspension and retain their reactivity.

Application of green zero-valent iron nanoparticles to the remediation of soils contaminated with ibuprofen.

Zero-valent iron nanoparticles (nZVIs) are often used in environmental remediation. Their high surface area that is associated with their high reactivity makes them an excellent agent capable of transforming/degrading contaminants in soils and waters. Due to the recent development of green methods for the production of nZVIs, the use of this material became even more attractive. However, the knowledge of its capacity to degrade distinct types of contaminants is still scarce. The present work describes the study of the application of green nZVIs to the remediation of soils contaminated with a common anti-inflammatory drug, ibuprofen. The main objectives of this work were to produce nZVIs using extracts of grape marc, black tea and vine leaves, to verify the degradation of ibuprofen in aqueous solutions by the nZVIs, to study the remediation process of a sandy soil contaminated with ibuprofen using the nZVIs, and to compare the experiments with other common chemical oxidants. The produced nZVIs had nanometric sizes and were able to degrade ibuprofen (54 to 66% of the initial amount) in aqueous solutions. Similar remediation efficiencies were obtained in sandy soils. In this case the remediation could be enhanced (achieving degradation efficiencies above 95%) through the complementation of the process with a catalyzed nZVI Fenton-like reaction. These results indicate that this remediation technology represents a good alternative to traditional and more aggressive technologies.

Green production of zero-valent iron nanoparticles using tree leaf extracts.

The interest in zero-valent iron nanoparticles has been increasing significantly since the development of a green production method in which extracts from natural products or wastes are used. However, this field of application is yet poorly studied and lacks knowledge that allows the full understanding of the production and application processes. The aim of the present work was to evaluate the viability of the utilization of several tree leaves to produce extracts which are capable of reducing iron(III) in aqueous solution to form nZVIs. The quality of the extracts was evaluated concerning their antioxidant capacity. The results show that: i) dried leaves produce extracts with higher antioxidant capacities than non-dried leaves, ii) the most favorable extraction conditions (temperature, contact time, and volume:mass ratio) were identified for each leaf, iii) with the aim of developing a green, but also low-cost, method water was chosen as solvent, iv) the extracts can be classified in three categories according to their antioxidant capacity (expressed as Fe(II) concentration): >40 mmol L(-1); 20-40 mmol L(-1); and 2-10 mmol L(-1); with oak, pomegranate and green tea leaves producing the richest extracts, and v) TEM analysis proves that nZVIs (d=10-20 nm) can be produced using the tree leaf extracts.

Comparison of different models to estimate genetic parameters for carcass traits in a commercial broiler line.

The effect of genetic and non-genetic factors for carcass, breast meat and leg weights, and yields of a commercial broiler line were investigated using the restricted maximum likelihood method, considering four different animal models, including or excluding maternal genetic effect with covariance between direct and maternal genetic effects, and maternal permanent environmental effect. The likelihood ratio test was used to determine the most adequate model for each trait. For carcass, breast, and leg weight, and for carcass and breast yield, maternal genetic and permanent environmental effects as well as the covariance between direct and maternal genetic effects were significant. The estimates of direct and maternal heritability were 0.17 and 0.04 for carcass weight, 0.26 and 0.06 for breast weight, 0.22 and 0.02 for leg weight, 0.32 and 0.02 for carcass yield, and 0.52 and 0.04 for breast yield, respectively. For leg yield, maternal permanent environmental effect was important, in addition to direct genetic effects. For that trait, direct heritability and maternal permanent environmental variance as a proportion of the phenotypic variance were 0.43 and 0.02, respectively. The results indicate that ignoring maternal effects in the models, even though they were of small magnitude (0.02 to 0.06), tended to overestimate direct genetic variance and heritability for all traits.

Estimates of genetic trend for carcass traits in a commercial broiler line.

Data from the slaughter of 24,001 chickens that were part of a selection program for the production of commercial broilers were used to estimate genetic trend for absolute carcass (CW), breast meat (BRW), and leg (LW) weights, and relative carcass (CY), breast meat (BRY), and leg (LY) weights. The components of (co)variance and breeding values of individuals were obtained by the restricted maximum likelihood method applied to animal models. The relationship matrix was composed of 132,442 birds. The models included as random effects, maternal additive genetic and permanent environmental for CW, BRW, LW, CY, and BRY, and only maternal permanent environmental for LY, besides the direct additive genetic and residual effects, and as fixed effects, hatch week, parents' mating group and sex. The estimates of genetic trend were obtained by average regression of breeding value on generation, and the average genetic trend was estimated by regression coefficients. The genetic trends for CW (+6.0336 g/generation), BRW (+3.6723 g/generation), LW (+1.5846 g/generation), CY (+0.1195%/generation), and BRY (+0.1388%/generation) were positive, and they were in accordance with the objectives of the selection program for these traits. The genetic trend for LY (-0.0019%/generation) was negative, possibly due to the strong emphasis on selection for BRY and the negative correlations between these two traits.

[Assessment of the penetration of culture media in uterine cavity as an effect of cervical lavage before embryo transfer: prospective and observational study of samples obtained in hysterectomy]. / Evaluación de la penetración del medio de cultivo a la cavidad uterina como efecto del lavado cervical previo a la transferencia embrionaria: estudio prospectivo y observacional en piezas obtenidas por histerectomía.

Cervical lavage used to remove and cleaning some of the scale elements as well as cervical mucous during embryo transfer has been a regular practice in many reproductive centers worldwide. However, the microenvironment influence using these techniques will or not be detrimental in the embryo development. Under this issue, a prospective study was doing in 16 patients (underwent hysterectomy). A cervical lavage was performed previous to the procedure similar to the embryo's transfer step, subsequently cervical invasion was checking. The age was 36.4 +/- 8.6 years, preoperatory diagnosis was abnormal uterine bleeding (n = 4), myomata (n = 4), adenomiosis (n = 4), endometrial polyp (n = 3) and chronic pelvic pain (n = 1). Uterine weight was 127.5 +/- 55.4 g with a surgical time of 48.8 +/- 12.5 minutes. Medium in the uterine cavity was founded in only one case. We believe that cervical lavage is a secure technique in embryo transfer.

Mechanism and kinetics of metal ion-mediated degradation of fosinopril sodium.

Fosinopril sodium (I), a new angiotensin converting enzyme inhibitor, is a diester prodrug of the active moiety II. We report here a novel transformation of fosinopril into beta-ketoamide, III, and a phosphonic acid, IV, mediated through metal ion participation. The interaction of fosinopril with magnesium ions was studied in a solution model system in which methanol was used as the solvent and magnesium acetate as the source of metal ions. Kinetic analysis indicated the degradation to be a bimolecular process, with the rate being first order in both metal ion and fosinopril concentration. The degradation products II, III, and IV effectively retarded the magnesium ion mediated reaction of fosinopril. Based on the results of 31P-NMR, 1H-NMR, Mn(II)-EPR spectroscopy experiments and mass spectrometry, a mechanism is postulated for this transformation. A key reactive intermediate has been characterized that supports the proposed mechanism. The results can account for the observed degradation profile of the fosinopril sodium in a prototype tablet formulation.

Mature presacral sacrococcygeal teratoma associated with a sacral "epignathus".

We report an example of sacrococcygeal teratoma presenting as a "supernumerary limb" in the left gluteal area with a rudimentary hemipelvis, femur, tibia, fibula, and tarsal bones. This monocephalus tripus dibrachius-appearing complex with associated with a deep seated but separate pararectal mature teratoma. This combination of a well-developed external limb with a deep but separate teratoma has been described.

Cocaine use and acute rupture of ectopic pregnancies.

The hemodynamic changes associated with ingestion of cocaine may precipitate rupture of ectopic pregnancy. Two cases are presented in which this association was suspected. We believe this to be the first report of this clinical entity, representing a risk factor that should be identified in patients with suspected ectopic pregnancy.

Synthesis of 2-(alkylamino)-5,6- and -6,7-dihydroxy-3,4-dihydroquinazolines and evaluation as potential dopamine agonists.

Based upon the known dopaminergic properties of 2-aminodihydroxy-1,2,3,4-tetrahydronaphthalenes (ADTN's), heterocyclic congeners were prepared. Several 2-(alkylamino)-5,6- and -6,7-dihydroxy-3,4-dihydroquinazolines were synthesized and tested for a dopamine-like vasodilatory action in the canine renal artery. The 6,7-disubstituted series had a weak antagonist effect against dopamine. Neither 5,6- nor 6,7-dihydroxy substitution gave dopamine agonists. Measured pKa values confirmed the expectation that the dihydroquinazolines were more basic than dopamine, one possible reason for the lack of dopamine-like action.

The interaction of hemispheric preference, laterality, and sex in the perception of emotional tone and verbal content.

Twenty male and 20 female subjects, divided into those who showed a right or left hemispheric preference, listened to auditory messages with conflicting verbal content and emotional tone. The messages were presented to each ear to determine whether the effect of hemisphere of input on the evaluation of the messages was modified by hemispheric preference. Except for left preference males, subjects responded on the basis of preference rather than laterality.

Synthesis and adrenergic blocking effects of 2-(alkylamino)-3,4-dihydroquinazolines.

Based on the known biological activity of a variety of guanidine-containing agents, several N-substituted 3,4-dihydroquinazolines were synthesized. These compounds can be considered to be rigid analogues of phenylguanidines. In anesthetized rats the compounds decreased blood pressure and were antagonists of the pressor response to norepinephrine.